STATE-OF-THE-ART REVIEW ARTICLE

Noninvasive Evaluation of

Roy Beigel, MD, Bojan Cercek, MD, PhD, Huai Luo, MD, PhD, and Robert J. Siegel, MD, Los Angeles, California

In current practice, right atrial pressure (RAP) is an essential component in the hemodynamic assessment of patients and a requisite for the noninvasive estimation of the pulmonary pressures. RAP provides an estimation of intravascular volume, which is a critical component for optimal patient care and management. Increased RAP is associated with adverse outcomes and is independently related to all-cause mortality in patients with cardiovascular disease. Although the gold standard for RAP evaluation is invasive monitoring, various techniques are available for the noninvasive evaluation of RAP. Various echocardiographic methods have been suggested for the evaluation of RAP, consisting of indices obtained from the inferior vena cava, sys- temic and hepatic veins, tissue Doppler parameters, and right atrial dimensions. Because the noninvasive evaluation of RAP involves indirect measurements, multiple factors must be taken into account to provide the most accurate estimate of RAP. The authors review the data supporting current guidelines, identifying areas of agreement, conflict, limitation, and uncertainty. (J Am Soc Echocardiogr 2013;26:1033-42.)

Keywords: Right atrial pressure, , , Noninvasive evaluation, Echocar- diography

the vertical distance from the top of the fluid in the manometer The terms ‘‘central venous pressure’’ (CVP) and ‘‘right atrial pres- (which was used at that time to measure CVP) always came to lie sure’’ (RAP) are synonymous as long as no obstruction of the vena within 1 to 2 cm of the sternal angle. Currently, examination of JVP cava is present. The gold standard for the evaluation of RAP is invasive is the mainstay of the bedside estimation of CVP.5,12,13 monitoring using a . Yet this is an invasive Evaluation of CVP using the jugular veins is preferably done using method not without risks1-3 and is thus not practical for widespread 4 the right-sided jugular vein, which is in direct line with the right , appli-cation. The normal range for RAP is between 1 and 7 mm Hg. and clinical assessment of CVP on the left may be marginally higher Elevated values have prognostic implications for both morbidity and than that on the right.14 Both the external jugular vein and the internal mortality,5-8 making the accurate assessment of RAP a determining 9,10 jugular vein (IJV) can be used for evaluation. Although the external factor in patient assessment, management, and outcomes. The jugular vein is easier to visualize, the IJV is preferred because it does noninvasive evaluation of RAP, also a crucial component of the not have valves and is in line with the superior vena cava (SVC) noninvasive estimation of the pressures, includes and the right atrium.15 The patient should be recumbent with the the physical examination along with Doppler echocardiographic head elevated at 30 to 45. The level of venous pressure is estimated indices. by identifying the highest point of oscillation of the jugular vein (which occurs during the expiratory phase of respiration). This level is then related to the middle of the right atrium, where venous pres- PHYSICAL EXAMINATION sure is, by convention, zero. A reliable substitute is the angle of Louis (JVP) at the junction of the manubrium and the body of the sternum, lo- Sir Thomas Lewis, in 1930, first proposed the determination of a pa- cated 5 cm above the middle of the right atrium (in approximation tient’s venous pressure during the physical examination.11 Lewis ob- for practical purposes). The vertical distance (in centimeters) from served that the top of the jugular veins of normal individuals and the sternal angle to the top of the jugular venous wave represents the JVP (Figure 1); thus, CVP equals JVP + 5 cm.14 Because the clav- icle lies vertically 2 cm above the sternal angle, only a CVP of 7 cm will From The Institute, Cedars-Sinai Medical Center, Los Angeles, California. be observed. JVP estimation may be inaccurate if the jugular vein is Dr. Beigel is a recipient of a fellowship grant from American Physicians and Friends constricted or torturous, and it might be difficult to assess in patients for Medicine in Israel (Boston, MA). with short necks, with prior neck surgery, or with prior catheter place- ment in the jugular vein. Attention ASE Members: ASE has gone green! Visit www.aseuniversity.org to earn free CME through an online activity related to this article. Certificates are available for immediate access upon successful completion of the activity. Non-members will need The Abdominojugular Reflux to join ASE to access this great member benefit! The test consists of assessing JVP before, during, and after abdominal compression. It is performed with firm pressure of 20 to 30 mm Hg Reprint requests: Robert J. Siegel, MD, The Heart Institute, Cedars-Sinai Medical applied to the midabdomen for 10 to 30 sec.16 The CVP of normal Center, 8700 Beverly Boulevard, Room 5623, Los Angeles, CA 90048-1804 individuals usually remains unchanged or does not increase by >4 (E-mail: [email protected]). cm for a beat or two (usually for <10 sec), or it may fall slightly.16,17 0894-7317/$36.00 If the CVP rises by >4 cm and stays elevated throughout the Copyright 2013 by the American Society of . maneuver, this correlates with elevated RAP.18 Reports suggest that http://dx.doi.org/10.1016/j.echo.2013.06.004 a positive result is indicative of right ventricular (RV) failure or 1033 1034 Beigel et al Journal of the American Society of Echocardiography September 2013

Abbreviations elevated pulmonary capillary wedge pressure.16 However, if ASE = American Society of the patient strains (Valsalva ma- Echocardiography neuver) during the test, it may BSA = Body surface area cause a false-positive result. In general, the physical exami- CVP = Central venous nation for the assessment of pressure RAP has limited accuracy com- DTI = Doppler tissue imaging pared with invasive19-24 or echocardiographic25,26 studies, IJV = Internal jugular vein most commonly underestimating IVC = Inferior vena cava JVP20-23 in the setting of elevated CVP.23 19 JVP = Jugular venous Eisenberg et al. found pressure that after a baseline physical examination and assessment of Figure 1 Evaluation of JVP. With the patient lying at about 45 , RA = Right atrial CVP, catheter-derived CVP mea-  the highest point of pulsation of the jugular vein is identified (ar- RAP = Right atrial pressure surements differed significantly rowhead). This is then related to the angle of Louis, found at the from those obtained on clinical ex- junction of the manubrium with the body of the sternum (aster- RV = Right ventricular amination in 50% of patients, and isk). The vertical distance to the top of the jugular venous SVC = Superior vena cava in 58% of these, the treatment wave (arrow) can be determined and reported, in centimeters, plan was changed on the basis of as the JVP. 3DE = Three-dimensional the invasive assessment of CVP. echocardiography Consequently the use of the phys- as well: IVC diameter and area are consistently largest when the 2DE = Two-dimensional ical examination might be best for patient is evaluated in the right lateral position, intermediate in the echocardiography categorizing CVP as either low to supine position, and smallest in the left lateral position.29 Patient po- VTI = Velocity-time integral normal or elevated. sition, therefore, is an important factor to consider when correlating IVC size and shape with hemodynamic variables. 30 Doppler In 1979, Natori et al. first described measuring IVC diameter and Echocardiography its change during respiration. Several studies have evaluated the corre- lation between RAP and different IVC parameters30-41 (Table 1). Doppler echocardiography is routinely used to noninvasively esti- However, fewer studies have evaluated the validity of the suggested mate RAP. The Doppler echocardiographic methods to estimate IVC parameters for the accuracy of the estimation of RAP.35,39,41 RAP include assessment of the inferior vena cava (IVC), SVC, and he- Most, but not all,29,31 studies have demonstrated good correlations patic vein indices of size and flow; Doppler systemic venous flow; tri- between the IVC collapsibility index ([IVCmax IVCmin]/IVCmax) cuspid valve Doppler inflow; tricuspid valve tissue Doppler; and 30,33-35,39 À and RAP (0.57 < r # 0.76). Although there is a correlation evaluation of right atrial (RA) dimensions. However, in uncommon between IVC diameter and RAP (0.72 < r # 0.86),29,31,35,40 some circumstances, the flow into the right atrium and consequently the reports suggest that the correlation found between IVC diameter Doppler velocities may be affected by RA compression or distortion, and RAP does not permit it to be used for the reliable estimation of as well as in the setting of RV inflow obstruction due to tumor or tri- RAP,31,33 because of the variability and overlap between patients cuspid stenosis. In these situations, assessing the tricuspid gradient can with normal RAPs and those with elevated RAPs. It is hypothesized be useful for the estimation of RAP. that an increase of RAP beyond a certain level may cause only minimal increases in IVC diameter and the degree of IVC collapsibility with inspiration. Thus, IVC dimensions and IVC Indices collapsibility can be used to detect elevated CVP, but they have The IVC is a highly compliant vessel, and consequently its size and limited utility in identifying the magnitude of CVP elevation. dynamics vary with changes in CVP and volume. Blood flow from On the basis of several studies,33,35,37 the American Society of the superior and IVC into the right atrium is biphasic, with the largest Echocardiography (ASE) in 200542 recommended using maximal forward flow occurring during ventricular . In general, there is IVC diameter 1 to 2 cm from the junction of the right atrium and a reciprocal relationship between pressure and flow; when flow in- the IVC at end-expiration and the IVC collapsibility index to give creases (in the IVC as well as the right atrium), pressure decreases an estimate of RAP. This measurement is best obtained from the and vice versa. During inspiration (which produces negative intratho- subcostal view, with the IVC viewed in its long axis (Figure 2). racic pressure), vena cava pressure decreases and flow increases27,28 Measurements should be made with the patient lying supine (because (Figures 2A–2C). Because the vena cava acts as a capacitance reser- the left lateral position may underestimate maximal IVC diameter).29 voir, phasic increases in forward flow from the cava to the right atrium However, Brennan et al.41 evaluated the 2005 ASE recommendations are accompanied by decreases in vena cava size. The smallest IVC di- for assessing RAP42 and found that only 43% of patients were cor- mension is seen during ventricular systole. At low or normal RAPs, rectly classified. On the basis of the results of their study, they sug- there is systolic predominance in IVC flow, such that the systolic gested a new cutoff range that gives an estimation with range limits flow is greater than the diastolic flow. As RAP increases, it is transmit- of 5—10 mm Hg (Table 2). The newer 2010 ASE guidelines43 have ted to the IVC, resulting in blunting of the forward systolic flow, re- been revised as noted in Table 2. These parameters yield more accu- duced IVC collapse with inspiration, and eventually IVC dilatation rate results when estimating low or high RAP: IVC diameter < 2.1 cm (Figures 2D–2F). The size and area of the IVC are affected by position and collapse > 50% correlates with a normal RAP of 0 to 5 mm Hg. Journal of the American Society of Echocardiography Beigel et al 1035 Volume 26 Number 9

Figure 2 Echocardiographic evaluation of RAP using IVC dimension and collapsibility. Subcostal 2DE during expiration (A) and in- spiration (B) and M-mode echocardiography (C) demonstrating good inspiratory collapse (asterisk) of the IVC (arrow) in a patient with normal RAP and 2DE during expiration (D) and inspiration (E) and M-mode echocardiography (F) demonstrating no inspiratory collapse of the IVC in a patient with elevated RAP.

IVC diameter < 2.1 cm with < 50% collapse and IVC diameter this finding needs confirmation. Brennan et al.41 did not find that > 2.1 cm with > 50% collapse correspond to an intermediate RAP indexing the IVC to BSA improved accuracy over the standard IVC of 5 to 10 mm Hg. IVC diameter > 2.1 cm with < 50% collapse sug- measurement for RAP estimation, and the ASE 2010 recommenda- gests a high RAP of 15 mm Hg. The guidelines recommend using mid- tions43 do not recommend an IVC index related to BSA. range values of 3 mm Hg for normal and 8 mm Hg for intermediate The published data indicate that IVC size and collapsibility indices RAP. If there is minimal collapse of the IVC (<35%) and/or secondary are appropriate to define RAP as high or low and are not a method for indices of elevated RAP are present (Table 3, discussed next), the providing a precise numeric value. It should be noted that the IVC can guidelines recommend upgrading to the higher pressure limit (i.e., 5 be dilated in individuals with normal RAPs; Table 4 lists the common and 10 mm Hg in the cases of normal and intermediate RAPs, respec- causes of a dilated IVC in the setting of normal RAP.37,46 To tively). Patients with low compliance with deep inspirations may have overcome some of the limitations of RAP estimation through IVC diminished IVC collapse, and a ‘‘sniff’’ maneuver causing a sudden de- indices, additional Doppler echocardiographic parameters have crease in intrathoracic pressure and by that accentuating the normal been evaluated and proposed to better quantify RAP (Table 5), which inspiratory response might be required to differentiate those with are further discussed. true diminished IVC collapsibility from those with normal collapsibility. The validity of adjusting the evaluation of IVC size to body surface Systemic Venous Indices area (BSA) is controversial. Data correlating IVC size indexed mainly The central venous flow pattern seen in the vena cava, jugular, and to BSA are inconsistent and limited to only a few studies.31,33,41,44,45 hepatic veins is characterized as seen in Figure 3A by three distinct Mintz et al.31 indexed IVC size measurements to patients’ BSAs and waveforms when evaluated by Doppler. The first is the systolic found a correlation between IVC index and RAP, but they still con- wave (Vs), caused by RA relaxation and descent of the tricuspid cluded that the degree of correlation did not permit the use of the ring associated with RV systole. The second is the diastolic wave IVC for an accurate estimation of RAP. Moreno et al.33 found no cor- (Vd), which occurs during rapid ventricular filling when the tricuspid relation between RAP and IVC parameters, whether indexed to BSA valve is open. The third is a positive A wave, which occurs with RA or not (r < 0.25), whereas Cheriex et al.44 showed a good correlation contraction and represents reverse flow. The A wave is small and (r = 0.92) between IVC index and RAP for evaluating hydration status might not be present in normal individuals.47 In the majority of nor- in hemodialysis patients. Kosiak et al.45 developed an alternative index mal adults, inspiration increases the magnitude of Vs and Vd, whereas consisting of the IVC/aorta ratio for evaluating patients’ volume status the A wave, if present, decreases in size.47 At low or normal RAPs, in the emergency department. They found in 52 healthy volunteers there is systolic predominant venous flow, such that the velocity of that IVC and aorta diameters significantly increased after fluid intake Vs is greater than the velocity of Vd (Figure 3A). As demonstrated and proposed an IVC/aorta index of 1.2 6 2 SD for SD = 0.17 as a ref- in Figure 3B, with elevation of RAP, the systolic flow predominance erence value for the healthy population aged 20 to 30 years; however, is lost, such that Vs is substantially decreased, and Vs/Vd is <1. The 1036 Beigel et al Journal of the American Society of Echocardiography September 2013

Table 1 Findings from major studies evaluating the correlation between IVC and RAP

Number of Timing of invasive and Study patients noninvasive evaluation Major findings

30 Natori et al. 14 NA IVCCI was inversely proportional to CVP when >10 cm H2O Mintz et al.31 111 NA IVC EDD normalized to BSA was correlated with RAP (r = 0.72) IVC EDD > 10 mm/m2 predicted elevated RAP (predictive accuracy, 94%) IVCCI was not correlated with RAP Moreno et al.33 175 <24 h IVC diameter was poorly correlated with RAP (r # 0.4) IVCCI was correlated with RAP (r = 0.71) Nakao et al.29 83 <24 h IVC diameter (r = 0.85) and area (r = 0.89) were correlated with RAP IVC diameter > 10 mm predicted elevated RAP (>8 mm Hg) (sensitivity, 84%; specificity, 96%; predictive accuracy, 95%) when measured in the left lateral position IVCCI was not correlated well with RAP and was more affected by IVC size than by RAP Simonson et al.34 27 Simultaneous Poor association between maximal IVC diameter and RAP (r = 0.35) Good association between minimal IVC diameter and RAP (r = 0.56) IVCCI was inversely correlated with RAP (r = 0.57) À Kircher et al.35 83* <24 h IVCCI was correlated with RAP (r = 0.75); best sensitivity, specificity, and predictive accuracy for RAP < 10 and > 10 mm Hg when IVCCI was $50% IVC EDD was correlated with RAP (r = 0.71) Jue et al.37 49† Simultaneous IVC diameter at expiration was poorly correlated with RAP (r = 0.58) No correlation between IVC change and RAP (r = 0.13) IVC diameter # 12 mm predicted RAP # 10 mm Hg (sensitivity, 25%; specificity, 100%) Nagueh et al.39 35 Simultaneous IVCCI was correlated with RAP (r = 0.76) No good correlation for IVCCI with mechanically ventilated patients (r = 0.4) Ommen et al.40 71 Simultaneous IVC dimension was correlated directly with RAP (r = 0.74) Brennan et al.41 102‡ 61 h of invasive Five different classifications on the basis of IVC size and collapsibility (see Table 2) evaluation Using traditional ASE 2005 criteria,42 only 43% of patients were classified adequately Indexing IVC to BSA did not improve accuracy

EDD, End-diastolic dimension; IVCCI, IVC collapsibility index; NA, not available. *Patients on excluded; retrospective analysis. †All patients on mechanical ventilation. ‡Thirty percent of patients had undergone cardiac transplantation.

Table 2 Estimation of RAP using IVC parameters

ASE 2010 recommendations43 Brennan et al.41

IVC diameter (cm) and collapse (%) RAP range (mean) (mm Hg) IVC diameter (cm) and collapse (%) RAP range (mm Hg)

Normal: #2.1 and >50 0–5 (3) #2.1 and >55 <5 Indeterminate* 5–10 (8) #2.1 and 35–55 or >2.1 and >55 0–10 High: >2.1 and <50 10–20 (15) >2.1 and 35–55 10–15 >2.1 and <35 10–20 #2.1 and <35 Undetermined

*In cases which the IVC diameter and collapse do not fit the normal or high criteria. Preferably secondary indices of elevated RAP should be in- tegrated (see Table 3). higher the RAP, the lower the pressure gradient between these veins only 40% of patients. A subsequent study by the same group in 14 pa- and the right atrium, causing diminished forward systolic flow. This tients with restrictive ventricular physiology50 also showed that in pa- blunted gradient is present in patients with restrictive heart disease tients with elevated RAP, Vs/Vd was #1. A study by Ghio et al.51 also and elevated right-sided filling pressures.48-51 Sivaciyan and confirmed that SVC flow was closely related to RAP, with a normal Ranganathan48 demonstrated that the jugular venous flow pattern Doppler pattern identifying patients with normal RAPs, a predominant and its variation are closely related to RAP. Although Vs/Vd > 1 Vs pattern identifying those with slightly elevated RAPs (#8 mm Hg) was associated with normal RAP, those who demonstrated ratios (sensitivity, 69%; specificity, 81%), and a predominant Vd identifying # 1 had elevated RAPs. those with elevated RAPs (>8 mm Hg) (sensitivity, 52%; specificity, Appleton et al.49 found in healthy individuals that SVC flow was ob- 95%). Consistent with the initial study by Appleton et al.,50 the success tainable in all subjects, but hepatic vein flow imaging was adequate in rate reported in obtaining flow velocity curves from the SVC was Journal of the American Society of Echocardiography Beigel et al 1037 Volume 26 Number 9

Table 3 Indices of elevated RAP Using Doppler, the hepatic vein systolic filling fraction, which is the ratio of the velocity-time integrals (VTIs) (Vs VTI/[Vs VTI + Vd VTI]), Dilated IVC with diminished respiratory collapse can be obtained. A value < 55% was found to be the most sensitive  Tricuspid E/e0 ratio > 6 (86%) and specific (90%) sign of RAP > 8 mm Hg. With higher RAP,  Diastolic flow predominance in the SVC, jugular vein, or hepatic there was a decrease in systolic filling fraction.39 In this study, the best  veins model for the prediction of mean RAP was 21.6 24 hepatic vein Bulging interatrial septum to the left atrium À Â  systolic filling fraction. This was further validated in the same analysis Dilated right atrium  on a prospective population of 50 patients, with a good correlation (r = 0.89), but reproducibility was only moderate (r = 0.5) in an- 40 À other study. Importantly, hepatic vein flow velocities have been val- idated in mechanically ventilated patients (sensitivity, 86%; Table 4 Causes for IVC enlargement in the presence of specificity, 90%),39 provided that the velocities are averaged over normal RAP five or more consecutive beats and constitute at least one respiratory Prominent Eustachian valve cycle.43  Athletic training Thus, the use of systemic and hepatic vein flow parameters can  Large BSA serve as an alternative to IVC parameters in individuals in whom  Mechanical ventilation the IVC may appear enlarged despite normal systemic venous pres-  Narrowing of the IVC-RA junction sure, or when subcostal views may not be optimal. It should be re-  Web or tissue present in the IVC membered that atrial compliance and relaxation, severe tricuspid  regurgitation, and tricuspid annular descent affect flow patterns and 100% compared with 76% in the hepatic veins. Patients with severe make them less reliable. In addition, the presence of atrial fibrillation tricuspid regurgitation were excluded from this study because this or past cardiac surgery can cause the hepatic vein systolic flow to be 40,57 may cause altered flow patterns in the systemic veins. diminished regardless of RAP.

Jugular Venous Flow and JVP Tricuspid Doppler and Doppler Tissue Imaging (DTI) Several investigators have used ultrasonography of the jugular veins Maximum velocities of the tricuspid E and A waves are significantly to predict CVP. Although the external jugular vein is easier to visual- higher during inspiration than during expiration when measured ize, its tortuous course, competent valves, and small size might not ac- from the atrial side of the tricuspid valve. However, when measured curately reflect the transmission of pressure from the right atrium. The from the ventricular side in the apical four-chamber view, respiration right IJV is a large vessel that directly connects to the SVC, but when affects only the maximum velocity of the E wave, without greatly evaluated clinically, the IJV may be visible only 20% of the time.23 affecting the E/A ratio.58 In contrast to mitral flow, on which age Lipton52 observed and described sonographic patterns within the has an important effect, Pye et al.59 found that there was no significant IJV determining venous collapse between the supine, semiupright, correlation between any tricuspid flow parameter and age, although and upright positions and concluded that patients can be differenti- two smaller studies did find weak correlations.60,61 Scapellato ated as those with low (<10 mm Hg), high (>10 mm Hg), and ex- et al.62 used tricuspid Doppler to estimate RAP, finding a significant tremely high (>20 mm Hg) CVPs. Donahue et al.53 demonstrated correlation with RAP (r = 0.98). The highest positive correlation a good correlation (r = 0.82) between IJV end-expiratory diameter was found between RV filling acceleration rate and RAP. An acceler- and CVP in 34 supine patients. They determined with good accuracy ation rate > 560 cm/sec2 predicted RAP > 5 mm Hg with sensitivity whether a patient had low or high CVP. Simon et al.54 assessed right of 100% and specificity of 99%. On the basis of the data in this study, IJV vascular compliance and concluded that an increase in the cross- the authors developed a detailed formula for the calculation of RAP: sectional area of the right IJV of >17% during the Valsalva maneuver RAP = 1.263 + 0.01116 acceleration rate, and they confirmed this À 63Â ruled out elevated RAP. Deol et al.55 compared ultrasound collapse finding in another study. pressure with JVP obtained clinically and with CVP in a group of Tissue Doppler allows the recording of myocardial and annular ve- 38 patients, of whom 11 (29%) were mechanically ventilated. locities. The maximal early filling velocity through the tricuspid valve Although the ultrasound collapse pressure was capable of accurately during (E wave) increases with increasing RAP. Evaluation measuring JVP, it underestimated CVP, especially when CVP levels using DTI can measure the velocity of tissue relaxation of the lateral 64 were high, concluding that measuring the ultrasound collapse point tricuspid annulus in diastole (e0 wave; Figure 5). Nagueh et al. found (which reflects JVP) does not reflect true CVP. a strong relation between RAP and the E/e0 ratio (r = 0.75). They found that a high E velocity combined with a low e0, resulting in an E/e0 ratio > 6, signals an RAP > 10 mm Hg (Figure 5B). This correla- Hepatic Vein Dimensions, Flow Patterns, and Collapsibility tion was also accurate in patients with mechanical ventilation. Sade The right and left hepatic veins empty into the IVC at the level of the et al.65 reproduced these findings, showing a good correlation diaphragm and are best imaged by echocardiography from the between E/e0 ratio and RAP (r = 0.7), giving the formulation of subcostal view (Figure 4). The hepatic venous flow pattern is closely RAP = 1.62 E/e0 + 2.13, which was also applicable and a good indi- related to the central venous flow pattern47,51,53 (Figure 3B). Like cator of RAP in mechanically ventilated patients. In 12 patients who the IVC, as RAP rises, the hepatic veins dilate and collapse less with underwent several simultaneous measurements, this ratio was also inspiration. In one study, left hepatic vein diameter correlated well a valid indicator of RAP change, with an increase of >2 in the E/e0 ra- (r = 0.81) with the percentage increase in CVP.56 Imaging was ob- tio associated with an increase of $5 mm Hg in RAP. In patients who tained in 90% of patients, yet underestimation occurred when RAP have undergone cardiac surgery, tricuspid E/e0 ratio might not be as values exceeded 12 mm Hg. accurate for the estimation of RAP. A subsequent study by Patel 1038 Beigel et al Journal of the American Society of Echocardiography September 2013

Table 5 Methods for evaluation of RAP besides IVC evaluation

Number Timing of invasive and Method of patients noninvasive evaluation Major findings

Systemic veins Jugular vein pattern 3453 Simultaneous CVP categorized as high ($10 mm Hg) or low (<10 mm Hg) was correlated and collapsibility with IJV diameter (r = 0.82)* 6754 Within 1 h An increase of >17% IJV CSA during Valsalva maneuver ruled out elevated RAP (>12 mm Hg) (sensitivity, 90%; specificity, 74%; NPV, 90%; PPV, 60%) 38†,55 Simultaneous Ultrasound compression was correlated with JVP but underestimated CVP (r = 0.81–0.91 for JVP, r = 0.62–0.5 for CVP) Jugular venous flow‡ 8248 Within 1 d Vs > Vd was associated with normal RAP Vs # Vd was associated with elevated RAP Single diastolic flow was associated with elevated RAP SVC flow 4049 NA Defined the normal pattern of SVC flow (Vs > Vd) SVC flow§ 12051 Within 1 h 2 $ Vs/Vd $ 1 (normal) = RAP # 5 mm Hg (sensitivity, 86%; specificity, 78%) Vs/Vd >2 (predominant systolic) = RAP # 8 mm Hg (sensitivity, 69%; specificity, 81%) Vs/Vd < 1 (predominant diastolic) = RAP > 8 mm Hg (sensitivity, 52%; specificity, 95%) Hepatic veins Hepatic venous flow 4049 Within 12 hours Defined normal hepatic venous flow (Vs > Vd) 1450 Vs/Vd # 1 was associated with elevated RAP Left hepatic vein 3256 Simultaneous Left hepatic vein diameter was correlated well with RAP (r = 0.81) diameterjj 39 HVFF 35 Simultaneous >55% suggested RAP > 8 mm Hg (sensitivity, 86%; specificity, 90%){ 5039 Simultaneous RAP = 21–24 HVFF (r = 0.89) 40  # 71 Simultaneous Modest correlation with RAP (r = 0.5) À DTI Acceleration rate of 77 Simultaneous Acceleration rate was a predictor of RAP (r = 0.98) RV early filling62 Acceleration rate > 560 cm/sec2 predicted RAP > 5 mm Hg (sensitivity, 100%; specificity, 99%) 64 Tricuspid E/e0 ratio 62 Simultaneous E/e0 ratio > 6 suggested RAP > 10 mm Hg (r = 0.75)** 65 †† 89 Simultaneous RAP = 1.62 E/e0 +2.13 (r = 0.7) 4066 Immediately before No good correlation (r = 0.09)‡‡ obtaining invasive data Tricuspid E/A ratio 40‡‡,66 Immediately before Good correlation with RAP (r = 0.57)§§ obtaining invasive data RV rIVRT57 45 Within 45 min RV rIVRT< 59 ms was a predictor of RAP > 8 mm Hg (sensitivity, 80%; specificity, 88%; AUC, 0.994) RA dimensions 3D RAVi66 80‡‡ Immediately before 3D RAVi $ 35 mL/m2 + IVC $ 2 cm was accurate for identifying obtaining invasive data RAP > 10 mm Hg (sensitivity, 89%; specificity, 92%; accuracy, 88%)jjjj

AUC, Area under the curve; HVFF, hepatic vein systolic filling fraction; NA, not applicable; NPV, negative predictive value; PPV, positive predictive value; RAVi, RA volume index; rIVRT, regional isovolumic relaxation time. *Not applicable to mechanically ventilated patients. †Twenty-nine percent of patients were mechanically ventilated. ‡Not applicable to patients who had undergone cardiac surgery and patients with severe left ventricular . §Only patients with ejection fractions < 35% were included. Patients with severe tricuspid regurgitation were excluded. jjImaging was obtainable in 90% of patients. Underestimation occurred when RAP was >12 mm Hg. {Also validated for mechanically ventilated patients. Patients with severe tricuspid regurgitation were excluded. #Patients with mechanical ventilation or severe tricuspid regurgitation were not included. **Also validated for mechanically ventilated patients. ††Not applicable to patients who had undergone cardiac surgery. ‡‡Only patients with acute decompensated were included. §§Inflow parameters could be determined in only 43% of patients. jjjjAnalysis was not feasible in 18% of patients. et al.66 in patients with heart failure did not find a good correlation RV regional isovolumic relaxation time refers to DTI of the lateral between RAP and E/e0 ratio but did find a modest but significant tricuspid annulus in the apical four-chamber view and is measured as correlation with tricuspid E/A ratio (r = 0.57, P = .02). the time period between the end of systolic annular motion and the Journal of the American Society of Echocardiography Beigel et al 1039 Volume 26 Number 9

Figure 3 Doppler imaging of flow in systemic veins. Pulsed-wave Doppler echocardiography showing (A) flow velocity in the SVC of a normal adult with normal biphasic pattern of forward flow, with systolic flow velocity (S) greater than diastolic flow velocity (D) and S/D > 1 and (B) flow velocity in the hepatic vein in a patient with elevated RAP showing diminished S, increased D, and S/D < 1.

Figure 4 Evaluation of hepatic vein collapsibility. Subcostal view during (A) expiration and (B) inspiration showing inspiratory collapse of the hepatic vein (arrow) in a patient with normal RAP and no collapse of the hepatic vein during (C) expiration and (D) inspiration in a patient with elevated RAP.

onset of the e0 wave. Using this index, it was found that RV regional in patients on mechanical ventilation when the IVC collapsibility in- isovolumic relaxation time < 59 msec corresponds to RAP > 8 mm dex is inaccurate.64 Hg (sensitivity, 80%; specificity, 88%).57 Doppler and DTI can provide an additional alternative for RAP evaluation when subcostal views cannot be obtained and there is in- RA Dimensions ability to apply IVC and hepatic indices, as well as be used to corrob- Elevated RAP can lead to enlargement of the right atrium and in- orate the prediction of RAP using hepatic vein systolic filling fraction creases in RA dimensions. Using two-dimensional echocardiography 1040 Beigel et al Journal of the American Society of Echocardiography September 2013

Figure 5 Doppler evaluation of tricuspid inflow. (A) (Top) Tricuspid inflow velocity Doppler recording (E = 84 cm/sec). (Bottom) Tri- cuspid annular velocity (e0) using DTI is 15 cm/sec in a patient with normal RAP. The E/e0 ratio is <6. (B) (Top) Tricuspid inflow velocity Doppler recording (E = 57.5 cm/sec). (Bottom) Tricuspid annular velocity (e0) is 4.87 cm/sec in a patient with elevated RAP. The E/e0 ratio is >6, which suggests an elevated RAP of >10 mm Hg.

(2DE), RA size and volume can be assessed from many views but are most commonly determined using the apical four-chamber view.43 Three-dimensional echocardiography (3DE) provides tomo- graphic imaging of cardiac chambers and has the potential to be a more accurate modality for atrial volume quantification than 2DE and has been validated using magnetic resonance imaging.67,68 Although qualitative and two-dimensional echocardiographic measures of the right atrium (both size and volume) do not signifi- cantly correlate with RAP,39 Patel et al.66 hypothesized that 3DE might aid in the identification of patients with heart failure with ele- vated RAPs. In their study, assessing the utility of 3DE for the evalu- ation of elevated RAP, RA size by 2DE was only modestly correlated with RA volume by 3DE (r = 0.58, P < .001). However, right atrium volume by 3DE was found to correlate with RAP (r = 0.51, P < .001). Compared with the traditional assessment using an IVC diameter $ 2 cm and decreased respiratory collapse of <40%, 3DE-measured max- imal RA volume $ 35 mL/m2 combined with IVC diameter $ 2 cm resulted in improved sensitivity for the identification of RAP >10 mm Hg in the study validation group (sensitivity, 86%; specificity, 92%; accuracy, 88%).66

CONCLUSIONS Figure 6 Schematic presentation of the interplay among the various parameters available for noninvasive evaluation and de- Currently, there is no single ideal parameter for noninvasive RAP es- termination of RAP. timation. Using the most recent ASE criteria43 based on IVC Journal of the American Society of Echocardiography Beigel et al 1041 Volume 26 Number 9

parameters, it is most appropriate to categorize RAP into low (0–5 Braunwald’s heart disease: a textbook of cardiovascular medicine. 9th mm Hg), normal (6–10 mm Hg), or elevated (11–20 mm Hg). We be- ed. New York: Elsevier; 2012. pp. 107-25. lieve additional information from some of the methods discussed in 16. Ewy GA. The abdominojugular test: technique and hemodynamic corre- this review should aid in the better quantification of RAP. As noninva- lates. Ann Intern Med 1988;109:456-60. sive evaluation of RAP involves indirect measurements, multiple fac- 17. Matthews MB, Hampson J. Heaptojugular reflux. Lancet 1958;1:873-6. 18. Hultgren HN. The effect of increased venous return on the venous pres- tors must be taken into account to provide an accurate estimate of sure in patients with congestive heart failure. Am Heart J 1950;39: RAP. It is the interplay among these echocardiographic findings mea- 592-603. suring dynamic changes, flow, and dimensions that yields the best 19. 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